The Clinical Epilepsy Section (CES) is using a multimodality approach to evaluate patients with severe epilepsy, including simultaneous video and telemetered electroencephalographic (EEG) recording of seizures, daily determinations of antiepileptic drug serum concentrations, positron emission tomography (PET), magnetic resonance imaging (MRI), and magnetoencephalography_(MEG). A specific seizure diagnosis is established allowing each patient to be assigned to an appropriate research protocol and therapy. PET uses radiolabelled tracers to measure cerebral glucose metabolism, blood flow, and neurotransmitter distribution. Focal hypometabolism may underlie epileptogenic zones. During seizures, increased glucose utilization and blood flow is found. In the Lennox-Gastaut syndrome, PET has revealed the existence of two separate metabolic patterns despite clinical seizure similarity. MRI may show small structural lesions underlying PET hypometabolism even when computed tomography (CT) is normal. Further studies will elucidate the relation of metabolic and pathologic changes. MEG may have the potential to accurately localize the subsurface origin of spikes. EEG provides little information on the spatial distribution of epileptiform discharges in cortical depths; MEG may be superior. Digital signal processing is being applied to data from multiple closely spaced electrode arrays. Comparison of invasive localization of epileptic foci using subdural electrodes and noninvasive evaluation is being performed. After surgery, patients are followed with serial clinical, neuropsychologic, and EEG evaluation. Children with partial seizures are followed with serial PET scans to assess the development of hypometabolism in the epileptic focus. The effect of the ketogenic diet is also being studied. Seizures in kindled and post cardiac arrest audio-sensitive rats are used to study patterns of neuronal damage and their relation to altered electrophysiology. Somatostatin neurons are selectively lost in the dentate hilus of patients with longstanding temporal lobe epilepsy. These neurons are vulnerable to non-NMDA but not NMDA mediated neurotoxicity in cell culture. NBQX, a non-NMDA antagonist, protected against loss of Somatostatin as well as NPY containing neurons, while MK-801 protected only against the former. Paired pulse inhibition was lost in both experimental groups. SS and NPY immunoreactive neurons may not be responsible for this type of inhibition.